Glycogen storage disease type Ia in Argentina: two novel glucose-6-phosphatase mutations affecting protein stability

Mol Genet Metab. 2004 Nov;83(3):276-9. doi: 10.1016/j.ymgme.2004.06.010.

Abstract

Glycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mutations have been identified. Two novel mutations, p.Thr16Arg (c.47C>G) located within the amino-terminal domain and p.Tyr209Cys (c.626A>G) situated in the sixth transmembrane helix, were uncovered in this study. Site-directed mutagenesis and transient expression assays demonstrated that both p.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argentina
  • Blotting, Western
  • COS Cells
  • Cricetinae
  • Cricetulus
  • DNA Mutational Analysis
  • DNA Primers
  • Female
  • Gene Deletion*
  • Gene Expression*
  • Glucose-6-Phosphatase / genetics*
  • Glucose-6-Phosphatase / metabolism
  • Glycogen Storage Disease Type I / genetics*
  • Glycogen Storage Disease Type I / metabolism
  • Humans
  • Male
  • Mutagenesis, Site-Directed
  • Mutation, Missense / genetics*
  • Phosphoric Monoester Hydrolases / metabolism

Substances

  • DNA Primers
  • Phosphoric Monoester Hydrolases
  • Glucose-6-Phosphatase

Associated data

  • OMIM/232200